The proposed project is a 5-year multicenter open-label trial designed to evaluate the efficacy of 40 kDa Pegylated interferon alfa-2a (Peginterferon alfa-2a) in combination with Ribavirin in the treatment of genotype-1 chronic hepatitis C (HCV, genotype-1) in African American men and women as compared to non-Hispanic whites. The Primary Aim of this proposal is to establish rates of sustained virologic response to a 48-week course of Peginterferon alfa-2a in combination with ribavirin in African Americans as compared to non-Hispanic whites with chronic HCV genotype 1 as assessed at the end of 48-week post-treatment follow-up by HCV RNA (<25 IU/mL). As Secondary Aims, we will assess biochemical markers of response to treatment [e.g., normalization of alanine aminotransferase (ALT)], specific patterns of early (e.g., early vs. no response over a 28-day period) and longitudinal (i.e., weeks 12 24, 36, 48 of treatment and week 24 post-treatment) response patterns, as well as, hepatic histology activity index (HAI), Body Mass Index (BMI) and demographic (e.g., age, gender, education, income level) and psychosocial factors (e.g., depression, anxiety, social support, coping) associated with treatment response and adherence. The Specific Aims of this project are as follows: PRIMARY AIM: SPECIFIC AIM 1. To establish rates of sustained virologic response to a 48-week course of Peginterferon alfa-2a in combination with ribavirin in African Americans as compared to non- Hispanics whites with chronic HCV genotype 1 as assessed at the end of 48-week post-treatment follow-up by HCV RNA (<25 IU/mL). SECONDARY AIMS: SPECIFIC AIM 2. To establish rates of sustained biochemical response to a 48-week course of Peginterferon alfa-2a in combination with ribavirin in African Americans as compared to non- Hispanic whites with chronic HCV genotype 1 as assessed at the end of 48-week post-treatment follow-up by serum ALT. SPECIFIC AIM 3. To determine patterns of longitudinal response or non response (i.e., weeks 12, 24, 36, 48 and 24 weeks post-treatment) of Peginterferon alfa-2a in combination with Ribavirin on: a) viral load (HCV RNA) alone; b) serum ALT alone; and c) combined HCV RNA and serum ALT. SPECIFIC AIM 4. To determine patterns of early (i.e., within a 28-day period) virologic response or non- response following Peginterferon alfa- 2a in combination with Ribavirin. SPECIFIC AIM 5. To evaluate changes in histology as determined by HAI by comparison of liver biopsy findings pre-treatment (within 12months prior to study initiation) and at the end of the 48-week post-treatment observation period. SPECIFIC AIM 6. To correlate end of treatment and sustained virologic response with baseline HAI, BMI and compliance to treatment. SPECIFIC AIM 7. To identify sociodemographic (e.g., age, education income, gender, ethnicity) and psychosocial (e.g., anxiety, depression, coping) predictors of adherence to treatment and virologic response to HCV RNA.